Zolbetuximab plus gemcitabine and nab-paclitaxel (GN) in first-line treatment of claudin 18.2-positive metastatic pancreatic cancer (mPC): Phase 2, open-label, randomized study.

Authors

Wungki Park

Wungki Park

Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY

Wungki Park , Eileen Mary O'Reilly , Junji Furuse , Chung-Pin Li , Do-Youn Oh , Rocio Garcia-Carbonero , Gaël Roth , Ho-Jin Lee , Futoshi Kunieda

Organizations

Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, Department of Medical Oncology, Kyorin University Faculty of Medicine, Mitaka, Japan, Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea, 12 de Octubre University Hospital, Madrid, Spain, Hepato-Gastroenterology Department, University Hospital of Grenoble, Grenoble, France, Astellas Pharma Inc., Northbrook, IL, Astellas Pharma, Inc., Tokyo, Japan

Research Funding

Pharmaceutical/Biotech Company

Background: GN is a first-line treatment option for patients (pts) with mPC. Poor prognosis and low 5-year survival rate ( < 5%) of pts with mPC highlight the need for new therapeutics. Claudin 18.2 (CLDN18.2), a tight junction protein expressed exclusively on normal gastric epithelial cells, is maintained during malignant transformation in gastric cancers and is frequently expressed in some carcinomas from organs that do not normally express it, such as pancreatic cancer. Zolbetuximab, a chimeric IgG1 monoclonal antibody, binds to CLDN18.2 and mediates tumor cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Methods: This phase 2 study (NCT03816163), expanded to enroll approximately 369 pts, will assess safety and efficacy of GN alone or with zolbetuximab in pts with histologically confirmed mPC and high CLDN18.2 expression (moderate-to-strong IHC staining intensity in ≥75% of tumor cells). The study included a safety lead-in that enrolled 3-12 pts to assess safety/tolerability of zolbetuximab (n = 3 at 1,000 mg/m2 on Cycle 1 Day 1 then 600 mg/m2 Q2W, then expand/de-escalate using a 3+3 design) plus GN. Dose-limiting toxicities (DLTs, defined as a specified zolbetuximab-related toxicity that occurs during DLT assessment period) will be assessed after Cycle 1 (28 days). Based on the recommended phase 2 dose (RP2D), confirmed during the safety lead-in, approximately 357 pts will be randomized 2:1 to zolbetuximab Q2W on Days 1 and 15 plus GN on Days 1, 8, and 15 of each cycle (Arm 1), or GN alone on Days 1, 8, and 15 of each cycle (Arm 2). Randomization will be stratified by ECOG performance status (0 or 1) and liver metastasis (yes or no). At sites in Japan, DLTs (assessed from Cycle 1 Day 1 to Cycle 2 Day 1) will be evaluated in ≤6 pts randomized to the RP2D in Arm 1. Pts will undergo imaging (CT/MRI) at baseline and every 8 weeks until investigator-assessed disease progression (RECIST v1.1) or the start of another systemic anticancer treatment, whichever comes earlier. In addition to confirming the RP2D during the safety lead-in, primary objectives are to assess whether treatment with zolbetuximab plus GN, versus GN alone, improves overall survival (randomization phase) and to establish the safety/tolerability profile of zolbetuximab plus GN (across the study). Secondary endpoints include progression-free survival, objective response rate, disease control rate, duration of response, pharmacokinetics, and health-related quality of life (per protocol amendment). Data will be presented using descriptive statistics for continuous endpoints and frequency and percentage for categorical endpoints. At original protocol enrollment completion (October 2021), 84 sites were actively recruiting; sites are currently reopening for screening/enrollment pending protocol amendment approval. Clinical trial information: NCT03816163.

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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Track

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Sub Track

Pancreatic Cancer

Clinical Trial Registration Number

NCT03816163

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr TPS4186)

DOI

10.1200/JCO.2022.40.16_suppl.TPS4186

Abstract #

TPS4186

Poster Bd #

158a

Abstract Disclosures